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Anemia is defined as a reduction in red cell counts, blood hemoglobin concentration or hematocrit per cubic millimeter. Initial diagnostic approach to the anemic patient includes a detailed history, physical examination and primary laboratory tests. The blood smear, direct Coombs test and reticulocyte counts are very helpful diagnostic tools in anemia. [ABSTRACT FROM AUTHOR]

Malignant rhabdoid tumor is a rare and malignant tumor of childhood. Generally it originates from the kidney and central nervous system, but occasionally it may arise from the orbit. Differential diagnosis from other childhood soft tissue sarcomas should be done. We report here an 8-week-old female infant with malignant rhabdoid tumor of the orbit who was treated with chemotherapy and surgery. The 8 week-old girl was referred to our hospital with a history of right proptosis first noted at birth. Physical and laboratory evaluation of the patient was normal except for right proptosis. The mass was removed surgically. Histopathologic examination and immunohistochemical findings of the specimen were evaluated as malignant rhabdoid tumor. Chemotherapy was administered. While in clinical remission, she succumbed during a febrile episode. Malignant rhabdoid tumor can rarely originate from the orbit. Malignant rhabdoid tumor should be kept in mind in the differential diagnosis of orbital masses, and surgery, chemotherapy and local radiotherapy should be used as combined therapy due to the poor prognosis. [ABSTRACT FROM AUTHOR]

Background: Malignant infantile osteopetrosis (MIOP) presents early in life with extreme sclerosis of the skeleton and reduction of bone marrow spaces. Since there is a defect in the bone marrow, the disease can cause anemia, extramedullary hematopoiesis secondary to anemia leading to hepatosplenomegaly, cranial nerves compression and severe growth failure. This disorder is often lethal within the first decade of life because of secondary infections. Stem cell transplantation (SCT) remains the only curative therapy. Case Presentation: We report a two-month old male infant, diagnosed as MIOP while investigating the cause of hepatosplenomegaly. The patient was referred for stem cell transplantation. Conclusion: Malignant infantile osteopetrosis should be kept in mind as a rare cause of hepatosplenomegaly and the patient should be referred for stem cell transplantation before neurologic or visual impairment develops. [ABSTRACT FROM AUTHOR]

Here we outline a practical approach to the detection of thalassemias in some clinical settings. Any patient with a low mean corpuscular volume (MCV) with or without anemia or a neonatal screening result indicating possible presence of thalassemia minor needs evaluation by a hematologist. But sometimes it is difficult to diagnose a patient whose hemoglobin electrophoresis is normal. We review the various types of the thalassemia syndromes, where exact diagnosis could be difficult. [ABSTRACT FROM AUTHOR]

Renal medullary carcinoma is a highly aggressive neoplasm of the kidney that originates from renal medulla and affects most commonly young adults and can also occur in children. The presentation is usually with hematuria, abdominal pain and less commonly with weight loss, fever and abdominal mass. The prognosis is dismal. The mean survival from time of the diagnosis is 3 months. A child with renal medullary carcinoma presenting with abdominal mass is described because this tumor is very rarely encountered in childhood and can be confused with yolk sac tumor histopathologically. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented concerning cases of malignancies associated with hemophagocytic syndrome (HPS) in children.

Quadricuspid aortic valve anomaly is a very rare congenital heart anomaly. Its incidence is 0.01-0.04 percent. This anomaly is characterized by the presence of four aortic valves of the same or different sizes. This may often lead to progressive aortic regurgitation or rarely aortic valve stenosis. In aortic valve evaluation with transthoracic echocardiographic, if a careful examination is not performed, the diagnosis of quadricuspid aortic valve may be overlooked or may be misdiagnosed as insidious acute rheumatic carditis. Here, we presented a 13-year-old patient with quadricuspid aortic valve who was admitted to another center with chest pain, and was mistakenly diagnosed with insidious rheumatic carditis due to the aortic regurgitation detected on his transthoracic echocardiographic examination. We aimed to draw attention to this rare congenital heart valve disease. [ABSTRACT FROM AUTHOR]

Aim: Respiratory syncytial virus is one of the most important causes of lower respiratory tract infections, with high mortality and morbidity in infants and children. It can cause airway inflammation, mucosal edema, and small airway collapse. Materials and Methods: We evaluated the clinical and demographic characteristics of newborns aged 0-30 days who were hospitalized in Yüzüncü Yıl University Neonatal Intensive Care Unit due to lower respiratory tract infections and whose respiratory syncytial virus test was positive between 15/December/2022 and 15/February/2023. Results: Between the specified dates, 29 patients diagnosed with lower respiratory tract infections were admitted to our neonatal unit. Of the oral/nasopharyngeal swab samples sent from all of these patients, one was positive for SARS-CoV-2, one for adenovirus, one for influenza A/B, and 18 (62%) respiratory syncytial virus. The weeks of the birth of the patients who were found to be positive for respiratory syncytial virus A/B were 36.72±1.48. The number of days they spent in the hospital was 6.72±1.6, 2(11.1%) patients required intubation, and 7(38.8%) patients required noninvasive respiratory support. One patient presented with convulsions at home, and cough and fever symptoms appeared on the second day of hospitalization. All patients recovered with oxygen support, hydration, and supportive treatment and were discharged. Conclusion: The most common cause in neonates was found to be a respiratory syncytial virus. Early diagnosis and treatment are important in patients with suspected lower tract viral infections. Unnecessary antibiotic use and the spread of the disease should be prevented by increasing access to viral tests. [ABSTRACT FROM AUTHOR]

The tumor suppressor protein 53 (TP53) gene is one of the most studied genes in cancer. Although TP53 variants are rare events in acute leukemia, recent observations showed that relapse samples might harbor TP53 variants. Here, we aimed to determine TP53 variants (hotspot region, exon 4–11) in childhood acute lymphoblastic leukemia (B and T-ALL) patients (n = 94) including diagnostic-relapse pairs (n = 15) by amplicon sequencing and evaluate the clinical impact of these variants. In total, nine different (E298*, R283C, R273H, L252F, C229F, I195T, E286G, c.955_956insC, and c.920-1G > C) variants were identified in 17 (18%) childhood ALL patients. c.(920-1G> C) splice site variant and c.(955_956insC) insertion were reported for the first time. In diagnose-relapse pair samples, we identified acquired and/or loss of TP53 variants in the samples at the time of relapse. TP53 variants were found to be more common in T-ALL (37%) than in B-ALL patients (9%). Pathogenic TP53 variants were associated with a shorter overall survival time (p = 0.001).TP53 variants were found to be associated with inferior outcomes in our cohort and can be an independent risk factor for poor prognosis in childhood acute leukemia patients. Identification of low-frequent variants with next-generation sequencing approaches enables better knowledge of the clonal dynamics of ALL. [ABSTRACT FROM AUTHOR]

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a heterogeneous malignancy and consists of several genetic abnormalities. Some of these abnormalities are used in clinics for risk calculation and treatment decisions. Patients with ZNF384 rearrangements had a distinct expression profile regardless of their diagnosis, BCP-ALL or mixed phenotype acute leukemia (MPAL) and defined as a new subtype of ALL. In this study, we screened 42 MPAL and 91 BCP-ALL patients for the most common ZNF384 fusions; ZNF384::TCF3, ZNF384::EP300 and ZNF384::TAF15 by using PCR. We identified ZNF384 fusions in 9.5% of MPAL and 7.6% of BCP-ALL. A novel breakpoint was identified in ZNF384::TCF3 fusion in one BCP-ALL patient. T-myeloid MPAL patients showed significantly lower ZNF384 expression compared to lymphoid groups. Patients with ZNF384r had intermediate survival rates based on other subtypes. Prognostic and patient-specific treatment evaluation of ZNF384 fusions in both ALL and MPAL might help to improve risk characterization of patients. [ABSTRACT FROM AUTHOR]

Introduction: Inherited factor VII (FVII) deficiency (FVIID) is the most common of inherited rare bleeding disorders. Other determinants of clinical severity apart from FVII level (FVIIL) include genetic and environmental factors. We aimed to identify the cut-off FVIILs for general and severe bleedings in patients with FVIID by using an online national registry system including clinical, laboratory, and demographic characteristics of patients. Methods: Demographic, clinical, and laboratory data of patients with FVIID extracted from the national database, constituted by the Turkish Society of Hematology, were examined. Bleeding phenotypes, general characteristics, and laboratory features were assessed in terms of FVIILs. Bleeding rates and prophylaxis during special procedures/interventions were also recorded. Results: Data from 197 patients showed that 46.2% of patients had FVIIL< 10%. Most bleeds were of mucosal origin (67.7%), and severe bleeds tended to occur in younger patients (median age: 15 (IQR:6-29)). Cut-off FVIILs for all and severe bleeds were 16.5% and 7.5%, respectively. The major reason for long-term prophylaxis was observed as central nervous system bleeding (80%). Conclusion: Our data are consistent with most of the published literature in terms of cut-off FVIIL for bleeding, as well as reasons for prophylaxis, showing both an increased severity of bleeding and younger age at diagnosis with decreasing FVIIL. However, in order to offer a classification similar to that in Hemophilia A or B, data of a larger cohort with information about environmental and genetic factors are required. [ABSTRACT FROM AUTHOR]

Introduction: The lymphoid enhancer factor 1 (LEF1) is a DNA‐binding transcription factor that functions in the Wnt signaling pathway. Increased LEF1 activity is associated with progression of several types of cancer including leukemia. Here, we investigated LEF1 isoform expression and genomic variations in acute lymphoblastic leukemia (ALL). Methods: LEF1 isoform expression was evaluated by quantitative real‐time PCR in 87 newly diagnosed childhood ALL patients and controls. Moreover, Western blot analysis was performed for detection of LEF1 expression and the hotspot region of LEF1 was screened by deep sequencing. Results: The LEF1 mRNA expression of B cell ALL patients was higher than the controls (LEF1‐total P =.011, LEF1‐long P =.026). Moreover, B‐ALL samples showing higher total LEF1 expression had significantly shorter relapse‐free survival (P =.008) and overall survival (P =.011). Although full‐length LEF1 expression was similar to the controls in T‐ALL, 50% (n = 15) of the ALL patients had increased full‐length LEF1 protein expression. Imbalance between short‐ and full‐length LEF1 isoforms may lead to cell survival in ALL. Beside the LEF1 activation, LEF1 gene variations were rarely observed in our cohort. Conclusion: The results indicate that the Wnt pathway may have a pathogenic function in a group of ALL patients and high LEF1‐total expression might be a marker for shorter relapse‐free survival time in B cell ALL. [ABSTRACT FROM AUTHOR]

Purpose: Recently, a new form of congenital neutropenia that is caused by germline biallelic loss-of-function mutations in the SMARCD2 gene was described in four patients. Given the rarity of the condition, the clinical spectrum of the disease has remained elusive. We here report a new patient with a novel frameshift mutation and compare our patient with the previously reported SMARCD2-mutant patients, aiming to provide a more comprehensive understanding of the natural course of the disease. Methods: Clinical and laboratory findings of all reported patients were reviewed. Next-generation sequencing was performed to identify the causative genetic defect. Data on the hematopoietic stem cell transplantation including stem cell sources, conditioning regimen, engraftment, graft-versus-host disease, and infections were also collected. Results: An 11-year-old female patient had a variety of infections including sepsis, deep tissue abscesses, otitis, pneumonia, gingivitis, and diarrhea since infancy. A novel homozygous mutation in SMARCD2 (c.93delG, p.Ala32Argfs*80) was detected. Bone marrow examination showed hypocellularity and decreased neutrophils with diminished granules and myeloid dysplasia, but no blast excess as in previously reported patients. The neutropenia was non-responsive even to higher doses of granulocyte colony-stimulating factor (G-CSF); therefore, the patient was transplanted at 10 years of age from a HLA-A allele–mismatched unrelated donor using a reduced toxicity conditioning regimen and recovered successfully. Compared with the previous four cases, our patient showed longer survival before transplantation without blastic transformation. Conclusion: Distinctive myeloid features and long-term follow-up including therapy options are presented for the newly described case of SMARCD2 deficiency. This disorder is apparent at infancy and requires early transplantation due to the unrelenting disease course despite conventional therapy. [ABSTRACT FROM AUTHOR]

Transfusion-dependent thalassemia (TDT) is a group of thalassemia syndromes that require regular blood transfusions for survival. It is unknown whether the sense of smell of patients with TDT is affected, and if so, whether smell loss has an adverse effect on quality of life (QOL). Olfactory thresholds were measured using Snap & Sniff wands. QOL was assessed via the Short Form-36 (SF-36) questionnaire. Forty-two TDT patients from the Thalassemia Center in Istanbul Medical Faculty were tested (mean age 26.6 years), along with 42 healthy controls (mean age 28.0 years). Mean olfactory sensitivity was lower in the TDT patients than the controls ( p < 0.0001). TDT was associated with lower mean QOL scores on the domains of physical function ( p < 0.0001), physical role limitation ( p = 0.011), and general health ( p < 0.0001). Within the TDT group, significant correlations were present between the threshold scores and physical function, physical role limitation, emotional role limitation, and general health. Patients with TDT are less sensitive to odors than healthy controls and the lower olfactory test scores are related to lower quality of life, suggesting that decreased smell function is an additional complication of this disease. [ABSTRACT FROM AUTHOR]

Aim Cervical lymphadenopathy (LAP) is a common sign and may raise fears about serious illnesses. The aim of our study was to evaluate the patients with cervical LAPs in a general pediatrics clinic setting, and to evaluate follow-up results for potential causes and risk factors for malignancies. Material and methods Two hundred-eighteen patients aged between 79.4 ± 46.7 months with LAP were enrolled in this prospective cohort study. The patients were examined in terms of demographics, clinical, radiologic and serologic aspects like Epstein–Barr virus (EBV), cytomegalovirus (CMV), parvovirus B19. A lymph node biopsy was performed in selected patients. The patients were followed-up for 8 weeks and risk factors for malignancy were evaluated. Results Seventy patients (41.3%) had specific etiology and 6 (2.7%) had malignant causes. The causes were as follows: 27% ( n = 59) infections; 2.7% ( n = 6) malignancies; 11.4% ( n = 25) other causes. EBV was responsible for 27% of infectious causes. The other common infectious etiologies were CMV 4.3%, parvovirus B-19 2.9%, and group-A beta-hemolytic streptococcus (GAS) 10.8%. Four of the six malignancies were lymphomas. Predictive factors for malignancy were having LAP larger than 30 mm, rubbery lymph node, high serum CRP and LDH values, no hilum in ultrasonography, and enlargement of lymph node in follow-up. High uric acid levels and leucopenia were also common in the malignancy group. Conclusion Etiology of cervical LAPs was diagnosed in 41.3% patients. Infectious causes were the most common cause with 27%. Malignancy was diagnosed in 2.7% and lymphoma was the most common malignancy. [ABSTRACT FROM AUTHOR]

The MN1 (Meningioma 1) gene is overexpressed in certain subtypes of acute myeloid leukemia (AML) and high levels of MN1 expression in mouse bone marrow cells results in myeloid leukemia. We showed that compared with control bone marrow (BM) MN1 expression was increased (2-fold or more) in 29 out of 73 (40%) pediatric B-cell acute lymphoblastic leukemia (B-ALL) patient BM. Additional analysis of MN1 expression in sub-groups within our cohort carrying different chromosome translocations showed that carriers of the good prognostic marker t (12;21)(TEL–AML1) ( n = 27) expressed significantly more MN1 than both healthy controls ( n = 9) ( P = 0.02) and the group carrying the t (9;22)(BCR–ABL) ( n = 9) ( P = 0.001). In addition, AML1 expression was also upregulated in 31 out of 45 (68%) B-ALL patient BM compared with control and there was a significant correlation between MN1 and AML1 expression ( r = 0.3552, P = 0.0167). Retroviral MN1 overexpression increased the colony forming activity of mouse Pro-B/Pre-B cells in vitro . Our results suggest that deregulated MN1 expression contributes to the pathogenesis of pediatric B-ALL. Further investigation into the clinical and biological significance of elevated MN1 expression in TEL–AML1 positive leukemia might provide insight into additional molecular mechanisms contributing to B-ALL and may lead to improved treatment options for patients. [ABSTRACT FROM AUTHOR]

Abstract: B-lineage acute lymphoblastic leukemia (B-ALL) is a common subtype of acute leukemia in children. PAX5 plays a central role in B-cell development and differentiation. In this study, we analyzed PAX5 expression levels, transactivation domain mutations/deletions in B-ALL patients (n =115) and healthy controls (n =10). Relative PAX5 mRNA levels were significantly increased in B-ALL patients (p <0.0001). PAX5 expression was also evaluated in three different B-ALL subgroups (pro B, Common B and Pre B ALL) and showed stage specific expression levels. Pro B (p =0.04) and pre B (p =0.04) patients showed significantly high PAX5 mRNA levels compared to stage specific controls. At least one deletion of exons 7–8 or 9 has been identified in the 41% of the patients. CD34 positivity in patients and presence of large deletions (Δ7/8/9) showed a significant correlation (p =0.05). None of our patients showed PAX5 point mutations, but two previously identified SNPs (rs3780135 and rs35469494) were detected. Our results support that PAX5 is a critical factor in B-ALL development and aberrant PAX5 expression especially at early stages may leads to leukemic transformation. [Copyright &y& Elsevier]

Background: In this study, the authors aim to describe the survival and clinical characteristics of 141 retinoblastoma cases treated at Cerrahpasa Medical Faculty, University of Istanbul, Istanbul, Turkey, between 1981 and 2004. Method: The authors retrospectively analyzed the clinical records of 141 children (177 eyes) diagnosed with retinoblastoma and treated between 1981 and 2004. Information on gender, laterality, age at diagnosis, presenting signs, spread of tumor, treatment modality, survival rate, and family history were collected. Results: A total of 105 cases (74.5%) were unilateral and 36 cases (25.5%) were bilateral. The mean age overall at the time of diagnosis was 25 months; in unilateral cases, 29 months; and in bilateral cases, 16 months. The most common presenting signs were leukocoria (116 cases, 82%), strabismus (14 cases, 10%) and proptosis (11 cases, 8%). A total of 28 cases had orbital extension, nine patients had central nervous system invasion, and five cases exhibited bone marrow involvement. In total, 16 patients (11%) had a family history of retinoblastoma. One case developed a secondary neoplasm. The 3 year cumulative survival rate of 141 patients was 89.69% (unilateral, 90.74%; bilateral 87.35% P = 0.9371, P > 0.05, log rank test). Conclusion: The study’s survival rate was similar to developed countries. The success in higher survival rates is based on the authors multidisciplinary team approach done by the same group and the support of the authors’ clinic and government in sponsoring the medical insurance of all patients. [ABSTRACT FROM AUTHOR]

• CDKN2A/2B alterations were the most common variants in diagnosed and relapsed B-ALL. • CDKN2A/2B alterations were associated with relapse feature. • CRLF2 copy number alterations enriched at non-relapsed B-ALL samples. • Early relapsed samples showed a highly dynamic clonal pattern. Genomic profiles of leukemia patients lead to characterization of variations that provide the molecular classification of risk groups, prediction of clinical outcome and therapeutic decisions. In this study, we examined the diagnostic (n = 77) and relapsed (n = 31) pediatric B-cell acute lymphoblastic leukemia (B-ALL) samples for the most common leukemia-associated gene variations CRLF2, JAK2, PAX5 and IL7R using deep sequencing and copy number alterations (CNAs) (CDKN2A/2B, PAX5 , RB1, BTG1, ETV6, CSF2RA, IL3RA and CRLF2) by multiplex ligation proximity assay (MLPA), and evaluated for the clonal changes through relapse. Single nucleotide variations SNVs were detected in 19% of diagnostic 15.3% of relapse samples. The CNAs were detected in 55% of diagnosed patients; most common affected genes were CDKN2A/2B , PAX5, and CRLF2. Relapse samples did not accumulate a greater number of CNAs or SNVs than the cohort of diagnostic samples, but the clonal dynamics showed the accumulation/disappearance of specific gene variations explained the course of relapse. The CDKN2A/2B were most frequently altered in relapse samples and 32% of relapse samples carried at least one CNA. Moreover, CDKN2A/2B alterations and/or JAK2 variations were associated with decreased relapse-free survival. On the other hand, CRLF2 copy number alterations predicted a better survival rate in B-ALL. These findings contribute to the knowledge of CDKN2A/2B and CRLF2 alterations and their prognostic value in B-ALL. The integration of genomic data in clinical practice will enable better stratification of ALL patients and allow deeper understanding of the nature of relapse. [ABSTRACT FROM AUTHOR]

Introduction: Epidemiologic studies on pediatric acute lymphoblastic leukemias (ALL) have been conducted to evaluate the possible risk factors including genetic, infectious and environmental factors with the objective of idenfying the etiology. Mannose-binding lectin 2 (MBL2) plays an important role in first-line immune defense. HLA DRB1 alleles play a role in presentation of peptides to T cells and in activation of the adaptive immune response., Objective: In our study, we aimed to investigate both the MBL2 gene variant and HLA-DRB1 alleles in pediatric ALL patients., Materials: In this study, 86 high-risk ALL patients and 100 controls were included. Polymerase Chain Reaction (PCR)-Restriction Fragment Length Polymorphism (PCR-RFLP) and PCR-sequence specific primer (SSP) methods were used for detection of polymorphism of the MBL2 and HLA-DRB1 alleles, respectively., Results: The frequency of the MBL2 AB genotype was lower in female ALL patients, compared to male ALL patients (p = 0.034). An association was found between the MBL2 BB genotype and DRB1*07 and among patients with the MBL2 BB genotype; those who also carried the DRB1*07 and *04 alleles were significantly higher than those without the DRB1*07 and *04 alleles. (p = 0.048, p = 0.022, respectively)., Conclusion: This is the first study suggesting that the MBL2 BB genotype in association with the DRB1*07 or co-inheritance of the HLA-DRB1*04 and HLA DRB1*07 may have an impact on the etiopathogenesis of the disease., Competing Interests: Conflicts of interest The authors declare that there is no conflict of interest for the study., (Copyright © 2023 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. All rights reserved.)

BACKGROUND Neonatal hypoxic-ischemic encephalopathy (HIE) is a significant cause of perinatal and postnatal morbidity and mortality worldwide. Catalase (CAT) activity detection is used to determine levels of inflammation and oxidative stress. Glutathione (GSH) is the most critical non-enzymatic endogenous antioxidant. Lipid peroxidation levels marked after hypoxia can be detected based on the level of malondialdehyde (MDA). Ischemia-modified albumin (IMA) is considered a biomarker for cardiac ischemia and is known to increase in the liver, brain, and kidney in states of insufficient oxygenation. We aimed to explain the results and relations between the oxidant and antioxidants to detail oxidant-antioxidant balance and cellular mechanisms. MATERIAL AND METHODS Serum levels of IMA and MDA, as an oxidative stress marker, and CAT and GSH, as antioxidant enzymes, were measured in first blood samples of 59 neonates diagnosed with HIE, with pH <7, base excess >12, and APGAR scores. RESULTS Neonates who were ≥37 weeks of gestation and had hypoxia were included. Compared with healthy newborns (n=32), CAT was statistically significantly lower in the hypoxia group (P=0.0001), while MDA serum levels were significantly higher in neonates with hypoxia (P=0.01). There was no difference between hypoxic and healthy neonates in GSH and IMA measurements (P=0.054, P=0.19 respectively). CONCLUSIONS HIE pathophysiology involves oxidative stress and mitochondrial energy production failure. Explaining the pathways between oxidant-antioxidant balance and cell death, which explains the pathophysiology of HIE, is essential to develop treatment strategies that will minimize the effects of oxygen deprivation on other body organs, especially the brain.

Objectives: In congenital hemolytic anemias (CHA), it is not always possible to determine the specific diagnosis by evaluating clinical findings and conventional laboratory tests. The aim of this study is to evaluate the utility of next-generation sequencing (NGS) and clinical-exome-based copy number variant (CNV) analysis in patients with CHA., Methods: One hundred and forty-three CHA cases from 115 unrelated families referred for molecular analysis were enrolled in the study. Molecular analysis was performed using two different clinical exome panels in 130 patients, and whole-exome sequencing in nine patients. Exome-based CNV calling was incorporated into the traditional single-nucleotide variant and small insertion/deletion analysis pipeline for NGS data in 92 cases. In four patients from the same family, the PK Gypsy variant was investigated using long-range polymerase chain reaction., Results: Molecular diagnosis was established in 86% of the study group. The most frequently mutated genes were SPTB (31.7%) and PKLR (28.5%). CNV analysis of 92 cases revealed that three patients had different sizes of large deletions in the SPTB and six patients had a deletion in the PKLR., Conclusions: In this study, NGS provided a high molecular diagnostic rate in cases with rare CHA. Analysis of the CNVs contributed to the diagnostic success., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: In patients with acute lymphoblastic leukemia (ALL), the risk of thromboembolism increases due to hemostatic changes secondary to the primary disease and due to treatment-related factors. In this multicenter study, we aimed to research the frequency of central nervous system (CNS) thrombosis occurring during treatment, hereditary and acquired risk factors, clinical and laboratory features of patients with thrombosis, treatment approaches, and thrombosis-related mortality and morbidity rates in pediatric ALL patients., Procedure: Pediatric patients who developed CNS thrombosis during ALL treatment from 2010 to 2021 were analyzed retrospectively in 25 different Pediatric Hematology Oncology centers in Türkiye. The demographic characteristics of the patients, symptoms associated with thrombosis, the stage of the leukemia treatment during thrombosis, the anticoagulant therapy applied for thrombosis, and the final status of the patients recorded through electronic medical records were determined., Results: Data from 70 patients with CNS thrombosis during treatment, out of 3968 pediatric patients with ALL, were reviewed. The incidence of CNS thrombosis was 1.8% (venous: 1.5 %; arterial: 0.03%). Among patients with CNS thrombosis, 47 had the event in the first 2 months. Low molecular weight heparin (LMWH) was the most commonly used treatment with a median of 6 months (min-max: 3-28 months). No treatment-related complications occurred. Chronic thrombosis findings occurred in four patients (6%). In five (7%) patients who developed cerebral vein thrombosis, neurological sequelae (epilepsy and neurological deficit) remained. One patient died related to thrombosis, and the mortality rate was 1.4%., Conclusion: Cerebral venous thrombosis and, less frequently, cerebral arterial thrombosis may develop in patients with ALL. The incidence of CNS thrombosis is higher during induction therapy than during other courses of treatment. Therefore, patients receiving induction therapy should be monitored carefully for clinical findings suggestive of CNS thrombosis., (© 2023 Wiley Periodicals LLC.)

Background: The study investigates the nutritional status in children with acute lymphoblastic leukemia (ALL) during chemotherapy treatment because nourishment is substantial, as much as chemotherapy in children with malignant diseases., Material and Method: We enrolled 17 children with ALL (between 1 to 16 year-old, mean age 6.03 ± 4.04 y) from 5 different centers in Istanbul between September 2013 and May 2014. Anthropometric data, prealbumin, B12, and folate levels were assessed, at diagnosis, after the induction phase of chemotherapy, and before maintenance phases of chemotherapy in a longitudinal and prospective study., Results: Patients remarkably lost weight at the end of the induction phase ( P =0.064) and regained this loss before maintenance chemotherapy ( P =0.001). At the end of induction chemotherapy serum prealbumin level ( P =0.002), weight for height ratios ( P =0.016), weight for age ratios ( P =0.019) significantly decreased. From the end of the induction phase to the beginning of maintenance chemotherapy, weight ( P =0.001) and weight for age ( P =0.017) significantly, and weight for height were remarkably elevated ( P =0.076). At the end of the induction phase, serum prealbumin levels were significantly lower ( P =0.048) and below laboratory reference values ( P =0.009) in children younger than 60 months compared with those older. Serum folate levels increased from the end of the induction phase to the beginning of the maintenance phase ( P =0.025). Serum vitamin B12 levels did not alter significantly., Conclusion: There is malnutrition risk at the end of the induction phase of the ALL-BFM chemotherapy regimen; therefore, clinicians should follow up on nutrition closely, especially in under 5-year-old patients. However, before the beginning of the maintenance phase, children start to gain weight, and obesity risk occurs. Thus , further studies are needed to evaluate nutritional status during childhood ALL chemotherapy., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Acute myeloid leukemia (AML) is a highly heterogeneous disease. Although patients can be classified into risk groups based on their genetic changes, the prognosis of disease within these categories varies widely. This situation raises the need to search for new molecular markers related to AML. Serine peptidase inhibitor Kazal type 2 ( SPINK2 ) has recently been reported to be upregulated in AML and associated with poor outcomes by meta-analysis and in a limited number of AML patients., Methods: We analyzed SPINK2 mRNA expression in 62 patients (45 adult and 17 pediatric) with AML and 11 cell lines using quantitative Real-Time PCR (qRT-PCR). SPINK2 protein level was determined using ELISA in cell lines., Results: We found that the expression of SPINK2 mRNA and protein levels in AML cell lines (HL60 and NB4) have increased compared to other cell lines (K562, Jurkat and NALM6, MCF7, HeLa, HUVEC, hFOB, 293T, U87). SPINK2 mRNA expression was upregulated in patients with AML compared to controls (p=0.004) and significantly lower in t(8;21)-positive patients compared to negative patients (p=0.0006)., Conclusions: Our results suggest that SPINK2 serves an important role in AML development. Further studies are needed to evaluate SPINK2 expression in AML patients with t(8.21) and investigate to clarify its prognostic value in various subgroups of AML., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Objective. Idiopathic hypogonadotropic hypogonadism in children is a disease leading to a puberty absence. Some hypothalamic and pituitary defects cause hypogonadotropic hypogonadism. Pituitary magnetic resonance imaging is routinely performed in these patients. In our study, we provide an information about pituitary pathologies associated with an idiopathic hypogonado-tropic hypogonadism in childhood. Methods. Twenty-two patients, who were admitted to the pediatric endocrine outpatient clinic of our hospital because of their undeveloped secondary sex characteristics during adolescence, were included in our study. Age, gender, history, physical examination findings, and laboratory tests were recorded in patients. Pituitary magnetic resonance imaging results were examined. The criteria for the diagnosis of hypogonadism were: absence of puberty or delayed puberty, clinical signs or symptoms of hypogonadism, and presence of low or normal gonadotropin levels. Results. In the present study, 22 patients were diagnosed with hypogonadotropic hypogonadism. The mean age of the patients was 15.90±1.09 years. Basal and stimulated luteinizing hormone and follicular stimulating hormone levels of the patients were found to be low. Prolactin, cortisol, adrenocorticotropic hormone, free thyroxine, and thyroid stimulating hormone levels were within normal limits in all patients. The pituitary magnetic resonance imaging revealed six patients with pituitary adenoma, one with empty sella turcica, and five with pituitary hypoplasia. Conclusions. The present data showed that in the presence of hypogonadotropic hypogonadism, the hypothalamic-pituitary abnormalities are more likely to be present in the children compared to the adult population. Thus, it can be strongly emphasized the importance of the pituitary imaging examination, especially in the idiopathic hypogonadotropic hypogonadism cases., (© 2023 Eda Celebi Bitkin et al., published by Sciendo.)

Background: Central nervous system fungal infections (CNSFI) are seen in patients with hematologic malignancies and have high morbidity and mortality. Because of their rarity, there is limited data on CNSFI in children with no established treatment protocols or guidelines., Materials and Methods: In this multicenter retrospective study, 51 pediatric patients with leukemia, 6 of whom had undergone bone marrow transplantation, with proven or probable CNSFI were evaluated. Fungal infections were defined as proven or probable based on European Organisation for Research and Treatment of Cancer criteria. Proven CNSFI was diagnosed by appropriate central nervous system (CNS) imaging or tissue sample findings in combination with positive microbiological results of cerebrospinal fluid. A positive culture, microscopic evidence of hyphae, a positive result of the galactomannan assays are defined as positive microbiological evidence. Probable CNSFI was defined as appropriate CNS imaging findings together with proven or probable invasive fungal infections at another focus without CNS when there is no other explanatory condition. Data was collected by using the questionnaire form (Supplemental Digital Content 1, http://links.lww.com/JPHO/A541 )., Results: Seventeen patients had proven, 34 patients had probable CNSFI. Headaches and seizures were the most common clinical findings. The median time between the onset of fever and diagnosis was 5 days. The most common fungal agent identified was Aspergillus . Sixteen patients received single-agent, 35 received combination antifungal therapy. Surgery was performed in 23 patients. Twenty-two patients (43%) died, 29 of the CNSFI episodes recovered with a 20% neurological sequelae., Conclusion: CNSFIs should be considered in the differential diagnosis in patients with leukemia and refractory/recurrent fever, headache, neurologicalocular symptoms, and a radiologic-serological evaluation should be performed immediately. Early diagnosis and prompt management, both medical and surgical, are essential for improving clinical outcomes., Competing Interests: The authors declare no conflict of interest.

Background and Aim: Oral mucositis (OM) is a common side effect of systemic chemotherapy (CT) in cancer patients. The aim was to evaluate the effect of low-level laser therapy (LLLT) for the treatment of CT-induced OM children., Patients and Methods: The study was carried out in 40 pediatric patients 3 to 18 years of age, who were hospitalized for the diagnosis of leukemia and underwent CT between June 1, 2019, and December 31, 2019. They were randomly divided into 2 groups with 20 cases in each group. The LLLT group was treated with GaAlAs diode laser (l): 830 nm (infrared), power: 150 mW, dose: 4.5 J/cm2 and the control group underwent bicarbonate treatment. Patients received intervention for 3 days. The grade of OM was clinically assessed by the World Health Organization (WHO) Common Toxicity Criteria Scale. Visual Analog Scale was used on the same days with OM grade to evaluate the pain status., Results: While there was no significant difference between the groups in terms of OM grade at the beginning of the treatment and on the first, second, fourth, and 11th days of the treatment, the average OM grade of the LLLT group was found to be statistically significantly lower on the third, fifth, sixth, and seventh days of the treatment. The Visual Analog Scale score of the LLLT group was statistically significantly lower compared with the control group at all examinations starting from the first day of treatment (P<0.05)., Conclusion: In the treatment of oral OM that occurs in children after CT, both standard care and LLLT treatment improve the grade and pain of OM., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Children with cancer have an increased risk for hepatitis B virus (HBV) infections due to chemotherapy-induced secondary immunodeficiency and frequent blood transfusions. The aim of this study is to evaluate the efficacy and safety of hepatitis B vaccination during the intensive induction chemotherapy in children with cancer found to be seronegative for hepatitis B on admission., Materials and Methods: Children newly diagnosed with cancer were evaluated for the presence of hepatitis B surface antigen (HBsAg) and antibody on admission. The children negative for both were included in the study. A super-accelerated vaccination scheme (3 booster doses at days 1-5, 8-12, and 28-33) was administered to these seronegative children concurrently with induction chemotherapy. Antibody response was checked 4-8 weeks after the last vaccination and 6 months after the end of the treatment., Results: Eleven out of 122 children were seronegative for hepatitis B on admission (9%). Acute lymphoblastic leukemia, lymphoma, and solid tumors were diagnosed in 5, 4, and 2 children, respectively. Complete seroconversion was achieved in 4-8 weeks after the last vaccination with high titers of anti-HBs antibody, and all patients remained antibody-positive until 6 months after the completion of chemotherapy., Conclusion: The risk of transfusion-related infections increases with a number of transfused products and donor exposures, and it is more significant for immunosuppressed children with hematologic and oncologic malignancies. Hepatitis B vaccination could safely be applied with brisk and sustained responses in this vulnerable population, based on the local epidemiological data.

The aim of the study was to analyze the characteristics of posterior reversible encephalopathy syndrome (PRES) cases treated at 10 different institutions in our country. Fifty-eight patients diagnosed with PRES were included in this study. The data of PRES cases from 10 departments of pediatric hematology/oncology were analyzed. The mean age of the patients at the time of diagnosis of PRES was 8.95±3.66 years. Most patients (80.4%) had a primary diagnosis of acute leukemia. Patients received chemotherapy (71.4%) and/or used steroids within 14 days before the diagnosis of PRES (85.7%). Hypertension was found in 83.9% of the patients. Twenty-six patients had infections and 22 of them had febrile neutropenia. The most common electrolyte disorders were hypocalcemia, hypomagnesemia, and hypopotassemia. Six patients had tumor lysis syndrome and 4 had inappropriate antidiuretic hormone syndrome. Magnetic resonance imaging was used for diagnosis in all patients. The most commonly involved regions by magnetic resonance imaging were occipital (58%), parietal (51%), and frontal lobes (45%), respectively. Twenty-five patients required intensive care and 7 patients were intubated. In conclusion, PRES may develop during the follow-up and treatment of hematological diseases. In addition to steroid and intense combined chemotherapies, immunosuppressive agents and hypertension are also factors that may be responsible for PRES., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Gynaecomastia in adolescents is a benign glandular proliferation of the male breast. Secondary causes of gynaecomastia in adolescents are relatively rare and may result from a wide variety of rare pathological conditions. Among these, klinefelter syndrome, complete androgen resistance, adrenal tumours and oestrogen-secreting testicular tumours, hypogonadism, hyperthyroidism, kidney disease and medications play a role in aetiology. The aim of our study is to review the demographic characteristics, hormone profile, aetiological characteristics of paediatric gynaecomastia patients admitted to a single center and to determine the frequency of pathological gynaecomastia. Forty-three male patients with gynaecomastia who applied to the paediatric endocrinology outpatient clinic were included in our study. Demographic characteristics, physical examination findings, hormone profile, breast ultrasonography and karyotype results of the patients were recorded. There were 43 male patients in our study. Thirty-six (83.7%) of the patients were pubertal gynaecomastia, 7 (16.2%) were pathological gynaecomastia. Three of the patients with pathological gynaecomastia were prepubertal gynaecomastia, 2 had klinefelter syndrome, 1 had hypergonadotropic hypogonadism after acute lymphoblastic leukaemia treatment and 1 had gynaecomastia after spirololactone use. Careful evaluation of patients with gynaecomastia is especially important in detecting pathological types. We reported the rare prepubertal gynaecomastia and klinefelter frequency in our study., (© 2021 Wiley-VCH GmbH.)

Objective: The objective of this study was to report the case of a girl diagnosed as suffering from multisystem, BRAF V600E-positive refractory Langerhans cell histiocytosis (LCH) and coexistent Erdheim-Chester disease (ECD) with perirenal, intracranial involvement and the dramatic response to clofarabine treatment., Observations: Histiocytoses are rare diseases with a broad clinical spectrum. Recent evidence supports a molecular and clinical overlap between LCH and ECD, and mixed LCH/ECD is now a separate entity. However, only a few pediatric cases of mixed disease have been reported in the literature., Conclusions: In a child with refractory, multisystem histiocytosis and atypical presentations, mixed LCH/ECD should be suspected in the differential diagnosis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction and Purpose: The Urinary Neutrophil-gelatinase associated lipocalin (NGAL) levels which are a biomarker for early diagnosis of kidney damage that may develop in patients with Polycystic Ovary Syndrome (PCOS) were investigated in the study., Material and Methods: The 30 patients diagnosed with Polycystic Ovarian Syndrome between the ages of 13 and 18 who applied to the Yuzuncu Yil University General Children's Outpatient Clinic were included in the PCOS group and 30 healthy adolescents without any known acute or chronic illness and drug use were included in the control group., Findings: Urine NGAL value was 842.204 ± 21.561 in PCOS group and 775.379 ± 23.98 in control group. NGAL level in PCOS group was statistically significantly higher than control group (p: .045). When we examine the relationship between dyslipidemia and PCOS; While dyslipidemia was positive in 10 (33.7%) patients in the PCOS group, it was negative in 20 (66.7%) patients. While 1 patient had dyslipidemia, 29 patients did not have dyslipidemia in the control group. A significant relationship was found between dyslipidemia and PCOS (p: .005)., Conclusion: We found that subclinical kidney dysfunction started in early stage patients in PCOS in our study. The urine NGAL level was thought to increase in response to increased oxidative stress in PCOS. We found no relationship between, insulin resistance and urea, BUN, creatinine and NGAL levels. However, we found a negative correlation between NGAL level and LDL. In addition, dyslipidemia, insulin resistance and ALT elevation were detected in the PCOS group.

Background: Chemotherapy with high dose methotrexate is the mainstay of treatment for Burkitt lymphoma (BL), especially to manage central nervous system (CNS) disease. However, methotrexate administration requires close drug level monitoring for appropriate folinic acid rescue, which might not be readily available in all centers. In this study, we assessed the long-term treatment outcomes of a modified Non-Hodgkin lymphoma (NHL)-Berlin-Frankfurt-Munster (BFM) 90 regimen in pediatric high-risk BL without CNS involvement., Methods: Between 1999 and 2011, 42 patients (median age: 7 years) with advanced-stage BL were treated with modified NHL-BFM 90 regimen (methotrexate at a dose of 1 g/m2). Demographic data, stage, lactate dehydrogenase (LDH) and treatment results were retrospectively evaluated. The patients were assessed for toxicity, survival and CNS recurrence., Results: Thirty-six patients had Stage III and six had Stage IV disease, respectively. The median LDH level was 1,432 IU/L. Four patients died of infectious and metabolic complications. One patient had local recurrence at the 48 < sup > th < /sup > month of the follow-up and he is in the second remission for 72 months. In Kaplan-Meier analysis, the overall survival and event-free survival rates at 10 years were found as 90 % and 88 %, respectively. None of our patients died of treatment failure., Conclusions: The administration of the reduced dose of methotrexate seems to not compromise treatment success nor increase the risk of CNS recurrence in high-risk BL without CNS involvement. The limitation of the study is that it is not randomized. Our treatment scheme might be considered for centers without methotrexate measurement facility.

Coagulation factor XIII (FXIII) is a fibrin-stabilizing factor with additional roles in wound healing and interactions between the decidua and fetus. Congenital FXIII deficiency is rare bleeding disorder. Inhibitor development against FXIII in inherited FXIII deficency is also uncommon, but may cause severe, life-threatening bleeding. FXIII is the last step in the coagulation cascade with normal coagulation paramaters (PT, aPTT), the detection of inhibitor to FXIII is quite difficult. The treatment of inhibitor-positive congenital FXIII deficiency is challenging due to the lack of a role of by-pass agents such as FVII. The best known ways of treatment in these cases are the use of high-dose FXIII concentrates and immunosuppression. Herein, we report the management of postoperative bleeding diathesis in a patient with FXIII deficiency who developed inhibitors, and to follow the clinical course of the disease with FXIII concentrate and immunosuppression.